Membrane-bound GTP-binding (G) proteins mediate signal transduction in a variety of cell systems. Although, the exact mechanisms of G protein action are still under investigation, G proteins appear to involve effectors located in the plasma membrane as well as other parts of the cell. WD-40 proteins contain a loosely conserved repeat of approximately 40 amino acids separated by a Trp-Asp dipeptide sequence which may recur several times within each polypeptide. The conserved core of the WD-40 sequence, which usually ends with the amino acids Trp-Asp (WD), was first identified in the .beta.-subunit of the heterotrimeric G protein, transducin. Several dozen WD-40 proteins have since been identified, none are enzymes, and all seem to have regulatory functions (Neer, E. J. et al. (1994) Nature 371:297-300).
Many of the WD-40 proteins are homologs of .beta.-transducin and function in signal transduction pathways within the cytoplasm. WD-40 proteins may participate in complex formation, and may interact with other G protein subunits through the WD-40 region. The .beta. subunit of G proteins enhances binding of the G.sub..alpha. subunit to receptors and assists in the assembly of the G-protein:receptor complex. The G.sub..beta..gamma. subunit binds to and brings the .beta.-adrenergic receptor kinase, .beta.-ARK, to the receptor (Touhara, K. et al. (1994) J. Biol. Chem. 269: 10217-10220).
A number of WD repeat proteins are localized to the nucleus and function in the repression of transcription. These include Tup1, Hir1, and Met30 in S. cerevisiae; SCON2 in Neurospora crassa; extra sex combs and Groucho in Drosophila; COP1 in Arabidopsis thaliana; and Rec14 in Schizosaccharomvces pombe. These WD-40 proteins turn off a wide variety of genes, including those involved in segmentation, sex determination, and neurogenesis, and those involved in photomorphogenesis.
The WD repeat protein, Rec14, is essential for meiotic recombination in S. pombe. Mutations in the Rec14 gene reduce meiotic recombination by as much as a factor of 1000 on chromosomes I and III. The Rec14 gene contains two exons separated by a 53-bp intron. The spliced transcript encodes a protein of 302 amino acids and contains six WD repeat motifs common in the G-beta transduction family and in S. cervisiae Rec103 protein. Rec103 mutations have no detectable effect on mitotic recombination. Based upon phenotypes and amino acid sequence similarities, it is possible that R is a functional homolog of S. cervisiae Rec103 (Evens, D. H. et al. (1997) Genetics 146:1253-1264). Autoantibodies occuring spontaneously in certain cancer patients are reagents for identifying cellular proteins, and it is the WD-40 motif in the beta-transducin proteins which target these antibodies.
The discovery of a new transducin beta-1 subunit and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of diseases associated with cell proliferation, in particular, cancers and immune response.